RECOVER-VITAL: Platform Protocol to Measure the Effects of Antiviral Therapies on Long COVID Symptoms

NCT ID: NCT05595369

Last Updated: 2025-12-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 963 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-07-26
• Study Completion Date: 2025-03-13

Brief Summary

This study is a platform protocol designed to be flexible so that it is suitable for a wide range of settings within health care systems and in community settings where it can be integrated into COVID-19 programs and subsequent treatment plans. This protocol is a prospective, multi-center, multi-arm, double-blind, randomized, controlled platform trial with different interventions organized as appendices to the protocol. Each appendix (or sub-study) evaluates potential mechanisms of action, efficacy, and safety of antivirals and other therapeutics in individuals with PASC, according to the platform protocol objectives. The hypothesis is that persistent viral infection, viral reactivation, and/or overactive/chronic immune response and inflammation are underlying contributors to PASC and that antiviral and other applicable therapies may result in viral clearance or decreased inflammation and improvement in PASC symptoms.

Detailed Description

Participants will be randomized to study interventions or placebo/controls based on the arms that are actively enrolling at the time of randomization. Study interventions may be added or removed according to adaptive design and/or emerging evidence. When there are multiple study interventions available, randomization will occur based on appropriateness of each intervention for the participant as determined by the study protocol.

Conditions

Long COVID; Long Covid19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Experimental: Paxlovid 25 day dosing

Drug: Paxlovid 25 day dosing Paxlovid (nirmatrelvir 300mg, ritonavir 100mg) bid x 25 days See NCT05965726 (Paxlovid Sub-study)

Group Type: EXPERIMENTAL

Experimental: Paxlovid 25 day dosing

Intervention Type: DRUG

Drug: Paxlovid 25 day dosing Paxlovid (nirmatrelvir 300mg, ritonavir 100mg) bid x 25 days See NCT05965726 (Paxlovid Sub-study)

Experimental: Paxlovid 15 day dosing

Drug: Paxlovid 15 day Dosing Paxlovid (nirmatrelvir 300mg and ritonavir 100mg) bid x 15 days then ritonavir 100mg bid plus nirmatrelvir matching placebo bid x 10 days See NCT05965726 (Paxlovid Sub-study)

Group Type: EXPERIMENTAL

Experimental: Paxlovid 15 day dosing

Intervention Type: DRUG

Drug: Paxlovid 15 day Dosing Paxlovid (nirmatrelvir 300mg and ritonavir 100mg) bid x 15 days then ritonavir 100mg bid plus nirmatrelvir matching placebo bid x 10 days See NCT05965726 (Paxlovid Sub-study)

Placebo Comparator: Control

Drug: Control ritonavir 100mg taken bid plus nirmatrelvir matching placebo bid bid x 25 days See NCT05965726 (Paxlovid Sub-study)

Group Type: PLACEBO_COMPARATOR

Placebo Comparator: Control

Intervention Type: DRUG

Drug: Control ritonavir 100mg taken bid plus nirmatrelvir matching placebo bid bid x 25 days See NCT05965726 (Paxlovid Sub-study)

Interventions

Experimental: Paxlovid 25 day dosing

Drug: Paxlovid 25 day dosing Paxlovid (nirmatrelvir 300mg, ritonavir 100mg) bid x 25 days See NCT05965726 (Paxlovid Sub-study)

Intervention Type: DRUG

Experimental: Paxlovid 15 day dosing

Drug: Paxlovid 15 day Dosing Paxlovid (nirmatrelvir 300mg and ritonavir 100mg) bid x 15 days then ritonavir 100mg bid plus nirmatrelvir matching placebo bid x 10 days See NCT05965726 (Paxlovid Sub-study)

Intervention Type: DRUG

Placebo Comparator: Control

Drug: Control ritonavir 100mg taken bid plus nirmatrelvir matching placebo bid bid x 25 days See NCT05965726 (Paxlovid Sub-study)

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. ≥ 18 years of age at the time of enrollment

2. Previous suspected, probably or confirmed SARS-CoV-2 infection, as defined by the Pan American Health Organization*

*Suspected and probable cases will only be allowed if it occurred before May 1, 2021, and will be limited to 10% of the study population. Otherwise, confirmed cases are required.

Suspected case of SARS-CoV-2 infection - Three options, A through C:

A. A person who meets the clinical OR epidemiological criteria. Clinical criteria: Acute onset of fever AND cough (influenza-like illness) OR Acute onset of ANY THREE OR MORE of the following signs or symptoms: fever, cough, general, weakness/fatigue, headache, myalgia, sore throat, coryza, dyspnea, nausea, diarrhea, anorexia. Epidemiological criteria: Contact of a probable or confirmed case or linked to a COVID-19 cluster; or

B. Acute respiratory infection with history of fever or measured fever of ≥ 38°C; and cough; with onset within the last 10 days; and who requires hospitalization); or

C. With no clinical signs or symptoms, NOR meeting epidemiologic criteria with a positive professional use or self-test SARS-CoV-2 antigen-Rapid Diagnostic Test.

Probable case of SARS-CoV-2 infection:

A. A patient who meets clinical criteria above AND is a contact of a probable or confirmed case or is linked to a COVID-19 cluster.

Confirmed case of SARS-CoV-2 infection - Two options, A through B:

A. A person with a positive nucleic acid amplification test, regardless of clinical criteria OR epidemiological criteria; or

B. Meeting clinical criteria AND/OR epidemiological criteria (See suspect case A). With a positive professional use or self-test SARS-CoV-2 Antigen-Rapid Diagnostic Test.

3. At least two moderate symptoms from the same symptom cluster or one severe cluster-associated symptom identified via the Cluster Targeted COVID-19 Symptom Questions (CTCSQ), with participant identifying new symptoms since COVID-19 illness and having persisted for at least 12 weeks

4. Meeting PRO Symptom Cluster criteria for at least one Symptom Cluster

5. Willing and able to provide informed consent, complete the surveys, clinical assessments, and return for all of the necessary follow-up visits

Exclusion Criteria

An individual who meets any of the following criteria will be excluded from participation in this study. Refer to appendices for additional appendix-level criteria:

1. Known active acute SARS-CoV-2 infection ≤ 4 weeks from consent

2. Known severe anemia, defined as < 8 g/dL

3. Meeting the following symptom cluster exclusion for all eligible clusters*:

a. Cognitive dysfunction: known stroke that resulted in cognitive impairment within 3 months of enrollment b. Autonomic dysfunction: atrial fibrillation or significant cardiac arrhythmia, more than moderate alcohol consumption**, pre-existing sustained severe hypertension (BP> 180/110 mmHg in the sitting position) c. Exercise intolerance: i. any of the following within 4 weeks of consent - an acute myocardial infarction or unstable angina, uncontrolled arrhythmias causing symptoms or hemodynamic compromise, acute myocarditis or pericarditis, uncontrolled acutely decompensated heart failure (acute pulmonary edema), acute pulmonary embolism, suspected dissecting aneurysm, severe hypoxemia at rest, any acute or chronic disorder that may affect exercise performance ii. if the participant is aggravated by exercise (e.g., infection, thyrotoxicosis, unable to cooperate)

** Defined as greater than 2 drinks a day for men and 1 drink a day for women. A drink is equivalent to 12 ounces of beer (5% alcohol content), 8 ounces of malt liquor (7% alcohol content), 5 ounces of wine (12% alcohol content), 1.5 ounces or a "shot" of 80-proof (40% alcohol content) distilled spirits or liquor (e.g., gin, rum, vodka, whiskey). 21

4. Known diagnosis of chronic Lyme disease with persistent symptoms, sequelae, or related therapy

5. Any non-marijuana illicit drug use within 30 days of informed consent

6. Current or recent use (within the last 14 days) of study intervention*

7. Known allergy/sensitivity or any hypersensitivity to components of the study intervention (s) or control*

8. Known contraindication(s) to study intervention(s),

9. Inability to discontinue symptomatic medications for the identified time periods

10. Moderate or severe immunocompromised patients, such as those described in the NIH COVID-19 Treatment Guidelines (https://www.covid19treatmentguidelines.nih.gov/ special populations/immunocompromised/)

11. Currently enrolled in another clinical trial outside this platform protocol or another study intervention appendix in this platform protocol***

***Participants may re-enroll in the trial for a different study intervention appendix if the participant has completed an appropriate washout period and efficacy has been determined for the appendix in which the participant was previously enrolled.

12. Any condition that would make the participant, in the opinion of the investigator, unsuitable for the study

• If only one study intervention appendix is open at the time of enrollment. If multiple study intervention appendices are open, a participant may be excluded from any study intervention appendix based on contraindications listed in the study intervention appendix, current use of study intervention, or known allergy/sensitivity/hypersensitivity and still remain eligible for the remaining study intervention appendices.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Kanecia Obie Zimmerman

OTHER

Sponsor Role: lead

Responsible Party

Kanecia Obie Zimmerman

Associate Professor of Pediatrics

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Kanecia Zimmerman, MD PhD

Role: STUDY_CHAIR

Duke University

Richard Whitley, MD

Role: STUDY_CHAIR

University of Alabama at Birmingham Medical Center

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

University of Arizona/Banner University Medical Center Phoenix

Phoenix, Arizona, United States

University of Arizona Banner Medical Center

Tucson, Arizona, United States

Cedars Sinai Medical Center

Los Angeles, California, United States

Hoag Memorial Hospital

Newport Beach, California, United States

University of California San Francisco General Hospital

San Francisco, California, United States

Stanford University

Stanford, California, United States

Los Angeles Biomedical Institute at Harbor-UCLA Medical Center

Torrance, California, United States

University of Colorado

Aurora, Colorado, United States

Howard University Hospital

Washington D.C., District of Columbia, United States

University of Florida College of Medicine Jacksonville

Jacksonville, Florida, United States

Lakeland Regional Medical Center

Lakeland, Florida, United States

Valencia Medical and Research Center

Miami, Florida, United States

Grady Memorial Hospital

Atlanta, Georgia, United States

Kaiser Permanente Southwood

Atlanta, Georgia, United States

Morehouse School of Medicine

Atlanta, Georgia, United States

Atlanta VA Medical Center

Atlanta, Georgia, United States

Emory Health Care

Decatur, Georgia, United States

Northwestern Memorial Hospital

Chicago, Illinois, United States

Rush University Medical Center

Chicago, Illinois, United States

University of Illinois at Chicago

Chicago, Illinois, United States

North Shore University Health System

Evanston, Illinois, United States

Koch Family Medicine

Morton, Illinois, United States

Methodist Medical Center of Illinois

Peoria, Illinois, United States

Saint Francis Medical Center

Peoria, Illinois, United States

University of Kansas Medical Center

Kansas City, Kansas, United States

University of Kentucky Chandler Medical Center

Lexington, Kentucky, United States

Johns Hopkins Hospital

Baltimore, Maryland, United States

Jadestone Clinical Research, LLC

Silver Spring, Maryland, United States

Tufts Medical Center

Boston, Massachusetts, United States

Brigham and Womens Hospital

Boston, Massachusetts, United States

Boston Medical Center

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Mayo Clinic

Rochester, Minnesota, United States

University of Mississippi Medical Center

Jackson, Mississippi, United States

Washington University School of Medicine

St Louis, Missouri, United States

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, United States

Rutgers University-Robert Wood Johnson Medical School

New Brunswick, New Jersey, United States

University of New Mexico Health Science Center

Albuquerque, New Mexico, United States

NYU Langone Health/Brooklyn Hospital

Brooklyn, New York, United States

St. Lawrence Health Medical Campus

Canton, New York, United States

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Weil Cornell Medicine

New York, New York, United States

University of North Carolina

Chapel Hill, North Carolina, United States

East Carolina University

Greenville, North Carolina, United States

Duke Clinical and Translational Science Institute

Kannapolis, North Carolina, United States

Wake Forest University

Winston-Salem, North Carolina, United States

Lillestol Research, LLC

Fargo, North Dakota, United States

University of Cincinnati Medical Center

Cincinnati, Ohio, United States

University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States

MetroHealth System

Cleveland, Ohio, United States

Cleveland Clinic

Cleveland, Ohio, United States

Oklahoma Clinical and Translational Science Institute

Oklahoma City, Oklahoma, United States

Oregon Health and Science University

Portland, Oregon, United States

UPMC Presbyterian Shadyside

Pittsburgh, Pennsylvania, United States

Avera McKennan Hospital & University Health Center

Sioux Falls, South Dakota, United States

Clinical Trials Center of Middle Tennessee

Franklin, Tennessee, United States

Houston Methodist Hospital

Houston, Texas, United States

University of Texas Health Science Center at Houston

Houston, Texas, United States

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Vermont Lung Center, University of Vermont

Colchester, Vermont, United States

University of Virginia

Charlottesville, Virginia, United States

Sentara Norfolk General Hospital

Norfolk, Virginia, United States

Swedish Health Services

Seattle, Washington, United States

University of Washington

Seattle, Washington, United States

Providence Medical Research Center

Spokane, Washington, United States

West Virginia Clinical and Translational Science Institute

Morgantown, West Virginia, United States

Froedtert Hospital-Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Hispanic Alliance for Clinical and Translational Research, Univ of Puerto Rico

San Juan, , Puerto Rico

Countries

United States; Puerto Rico

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Related Links

http://recovercovid.org/

Related Info

Other Identifiers

OTA-21-015G

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

Pro00111697

Identifier Type: -

Identifier Source: org_study_id